1. Field of the Invention
This invention relates to novel pyrimidinedione derivatives and acid addition salts thereof, to methods of producing the same and to pharmaceutical agents containing the same, which are effective for the treatment of cardiac dysfunctions such as arrhythmia and cardiac insufficiency.
2. Description of the Prior Art
The mechanism of the occurrence of arrhythmia is complicated. Abnormalities in stimulation production and disorders in the conducting system or combinations thereof are considered to be responsible.
As to disorders in excitation conduction, the re-entry theory is representative.
One of the conditions of occurrence of arrhythmia is irregularity in the refractory period in various parts of the heart. In addition, one-directional block, shortened refractory period, delay in conduction, the presence of circus movement are complicatedly involved.
Conventionally, varieties of antiarrythmic agents have been used for the treatment of arrhythmia.
The antiarrythmic agents are classified into four groups according to their mode of action.
Namely, E. M. Vaughan Williams (Vaughn Williams E. M.; "Advances in drug research, vol. 9", ed. by Harper N. J., Simmonds A. B., Academic Press, London, 1974; pages 69-101) classified the antiarrythmic agents into the following four groups according to their action against the action potential of cardiac muscle or against the ionic current which generates the action potential.
Class I: Sodium channel depressors
These agents are efficacious in repressing a sodium current. However, these agents have no or only minute effects on the retention time of the normal action potential and decrease the maximum rising velocity (V.sub.max) of the sodium current. The antiarrythmic agents which belong to this class have a high antiarrythmic activity but at the same time strongly repress cardiac functions. Careful consideration is required in administering to patients with cardiac failure or hypotension.
Class II: Beta-blocking agents
The agents in this class, represented by propranolol, are efficacious in the beta-blocking action and are useful in treating patients with arrhythmia in which the sympathetic nerve is involved. However, the care must be taken for use since these agents have side-effects caused by the beta-blocking action, such as depression of cardiac functions, induction of bronchial asthmatic attach and hypoglycemic seizures.
Class III: Pharmaceutical agents for prolonging the retention time of the action current.
These agents are efficacious in remarkably prolonging the retention time of the action current of the cardiac muscle and in prolonging an effective refractory period. Re-entry arrhythmia is considered to be suppressed by the action of the pharmaceutical agents of Class III. The medicaments of this Class III include amiodarone and bretylium. However, all the agents have severe side effects; therefore, careful consideration is required for use.
Class IV: Calcium antagonists
These agents control a calcium channel and suppress arrhythmia due to automatic sthenia of sinoatrial nodes and to ventricular tachycardia in which atrial nodes are contained the re-entry cycle.
Among these antiarrythmic agents, pharmaceutical agents of the Class III type are considered to be particularly important and the most efficacious, and known to be effective on ventricular arrhythmia, the most fatal of all symptoms.